Inflammation in Alzheimer's disease: Amyloid-β oligomers trigger innate immunity defence via pattern recognition receptors
Section snippets
Inflammation in the pathogenesis of Alzheimer's disease (AD)
There is a consensus that inflammation is involved in the pathogenesis of Alzheimer's disease (AD) (Neuroinflammation Working Group, 2000). However, the role of inflammation in the pathogenetic process is still a matter of debate, and it has been argued that neuroinflammation seems to be associated with AD pathology. One hundred years ago, Fischer (1910), according to Eikelenboom et al. (2006), proposed that the deposition of a peculiar foreign substance in the human cortex could induce a local
Innate immunity: guardian against pathogens and danger insults via pattern recognition receptors
Discrimination of self and non-self has been one of the fundamental forces in evolution, both in unicellular and multicellular organisms (Danilova, 2006). Host-defence has been based on the recognition of pathogen structures (Akira et al., 2006). Different strategies have evolved to recognize pathogen-associated molecular structures, abbreviated to PAMPs. Another requirement for successful evolution has been the sensing of the pathogen-free, self-derived danger signals and tissue injuries, in
Amyloid-β oligomers and fibrils trigger the inflammatory process in AD
Different research approaches have confirmed the central role of amyloid-β oligomers and fibrils in the pathogenesis of AD (Haass and Selkoe, 2007, Walsh and Selkoe, 2007, Tanzi and Bertram, 2005, Klein, 2002). The processing of amyloid-β precursor protein (APP) by β- and γ-secretases produces amyloid-β peptides, of which Aβ1–42 is especially toxic since it is spontaneously prone to undergo oligomerization and fibrillation processes. Recent studies have revealed that the soluble amyloid-β
Amyloid-β oligomers and fibrils activate innate immunity system via pattern recognition receptors
During the last decade, research on the innate immunity system has convincingly revealed that immune system not only fights against pathogens but also recognizes an abundance of DAMPs i.e. apoptotic and necrotic cells, accumulating aggregates, and aberrant cancer cell structures. Furthermore, cells under stress can secrete alarmins, such as HMGB1, S100 and HSPs, to alert the immune system (Bianchi, 2007). Brain cells, in particular astrocytes and microglial cells, contain a vast armament of
Alzheimer's pathology: outcome of the chronic activation of innate immunity defence?
A plethora of studies indicate that the production of amyloid-β peptides, especially Aβ1–42 peptide, is the triggering element in the pathogenesis of AD, as originally proposed in the amyloid cascade hypothesis (Hardy and Higgins, 1992). There are still controversies about how all the other hallmarks of AD originate from the β-cleavage of APP. In particular, how are the intracellular neurofibrillary tangles, containing hyperphosphorylated tau protein (Iqbal et al., 1993, Mandelkow and
Conclusions
AD is the progressive dementia which contains amyloid-β plaques and neurofibrillary tangles as pathological hallmarks. Inflammation is involved in the pathogenesis of AD but its role is under debate. Brain contains innate immunity system which is evolutionary conserved host-defence mechanism based on the recognition of foreign molecular patterns, either PAMPs or DAMPs. Glial cells and neurons contain a wide array of PRRs which sense amyloid-β species as DAMPs and trigger their clearance via
Acknowledgements
This study was financially supported by grants from the Academy of Finland and the University of Kuopio, Finland. The authors thank Dr. Ewen MacDonald for checking the language of the manuscript.
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